1,3-disubstituted/imidazolium salts

ABSTRACT

The imidazolium compounds of the formula ##STR1## wherein Q is arylene or heteroarylene, the group --NR 1  R 2  is a basic amino group, R 3  is lower alkylthio, lower alkoxy or the group --(A) n  --Ra, R 4  is a saturated or partially unsaturated lower hydrocarbon group, a basic amino group, --N═CRc--Rb, --CHRcRd, --NH--CHRcRd, --NH--CO--Re or --CHRc--CO--Re, R 5  is hydrogen, lower alkyl, lower hydroxyalkyl, lower alkoxyalkyl, lower haloalkyl, aryl or a fused benzene ring, R 6  is hydrogen or lower alkyl, Ra and Rb independently are aryl, heteroaryl or a basic amino group, Rc is hydrogen or lower alkyl, Rd is aryl or heteroaryl, Re is hydrogen, a saturated or partially unsaturated lower hydrocarbon group optionally attached via an oxygen atom, or an aryl, heteroaryl or basic amino group optionally attached via a lower alkyl group, A is vinylene or lower alkylene, n is the integer 0 or 1, the dotted line is an additional double bond and the symbol Y -   is a pharmaceutically acceptable anion, and their pharmaceutically acceptable acid addition salts, which possess valuable pharmacological properties are described. In particular, they possess antibacterial, antimycotic, protozoacidal and/or anthelmintic properties and are especially active against parasitic protozoa and worms. The compounds of formula I can be prepared according to known methods.

This is a division of application Ser. No. 07/046,473 filed May 4, 1987,now U.S. Pat. No. 4,814,332 issued Mar. 21, 1989.

BRIEF DESCRIPTION OF THE INVENTION

The present invention relates to imidazolium compounds of the formula##STR2## wherein Q is arylene or hetero-arylene, the group --NR¹ R² is abasic amino group, R³ is lower alkylthio, lower alkoxy or the group--(A)_(n) --Ra, R⁴ is a saturated or partially unsaturated lowerhydrocarbon group, a basic amino group or the group --N═CRc--Rb,--CHRcRd, --NH--CHRcRd, --NH--CO--Re or --CHRc--CO--Re, R⁵ is hydrogen,lower alkyl, lower hydroxyalkyl, lower alkoxyalkyl, lower haloalkyl,aryl or a fused benzene ring, R⁶ is hydrogen or lower alkyl, Ra and Rbindependently are aryl, heteroaryl or a basic amino group, Rc ishydrogen or lower alkyl, Rd is aryl or heteroaryl, Re is hydrogen, asaturated or partially unsaturated lower hydrocarbon group optionallyattached via an oxygen atom, heteroaryl or basic amino group optionallyattached via a lower alkyl group, A is vinylene or lower alkylene, n isthe integer 0 or 1, the dotted line is an additional double bond and thesymbol Y⁻ is a pharmaceutically acceptable anion, and thepharmaceutically acceptable acid addition salts thereof. The compoundsof formula I possess valuable pharmacological properties. In particular,they possess antibacterial, antimycotic, protozoacidal and/oranthelmintic properties.

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to imidazolium compounds of the formula##STR3## wherein Q is arylene or hetero-arylene, the group --NR¹ R² is abasic amino group, R³ is lower alkylthio, lower alkoxy or the group--(A)_(n) --Ra, R⁴ is a saturated or partially unsaturated lowerhydrocarbon group, a basic amino group or the group --N═CRc--Rb,--CHRcRd, --NH--CHRcRd, --NH--CO--Re or --CHRc--CO--Re, R⁵ is hydrogen,lower alkyl, lower hydroxyalkyl, lower alkoxyalkyl, lower haloalkyl,aryl or a fused benzene ring, R⁶ is hydrogen or lower alkyl, Ra and Rbindependently are aryl, heteroaryl or a basic amino group, Rc ishydrogen or lower alkyl, Rd is aryl or heteroaryl, Re is hydrogen, asaturated or partially unsaturated lower hydrocarbon group optionallyattached via an oxygen atom, heteroaryl or basic amino group optionallyattached via a lower alkyl group, A is vinylene or lower alkylene, n isthe integer 0 or 1, the dotted line is an additional double bond and thesymbol Y⁻ is a pharmaceutically acceptable anion, and thepharmaceutically acceptable acid addition salts thereof. The compoundsof formula I possess valuable pharmacological properties. In particular,they possess antibacterial, antimycotic, protozoacidal and/oranthelmintic properties.

Objects of the invention are the compounds of formula I and thepharmaceutically acceptable acid addition salts thereof; a process andintermediates for their preparation; the use of the intermediates forthe preparation of therapeutically active substances; the compounds offormula I and the pharmaceutically acceptable acid addition saltsthereof for use as therapeutically active substances; medicaments basedon compounds of formula I and their pharmaceutically acceptable acidaddition salts and their preparation; the use of these compounds in thecontrol or prevention of illnesses; as well as the use of the compoundsof formula I for the preparation of medicaments useful as antibacterial,antimycotic, protozoocidal and/or anthelmintic agents.

The term "lower", when used together with alkyl, alkoxy or alkylthio;denotes residues and compounds having 1 to 7 carbon atoms, preferably 1to 4 carbon atoms. The term "alkyl", taken alone or in combinations suchas "alkoxy" and "alkylthio", denotes, for example, straight-chain orbranched, saturated hydrocarbon residues such as methyl, ethyl,n-propyl, i-propyl, n-butyl, s-butyl, i-butyl, t-butyl and the like.

The term "saturated or partially unsaturated hydrocarbon group" denotesopen-chain and cyclic groups and combinations thereof. Examples ofsaturated and partially unsaturated lower hydrocarbon groups are: loweralkyl groups such as methyl, ethyl, propyl, i-propyl, s-butyl, i-butyland the like; lower alkenyl groups of 2 to 7 carbon atoms such as2-propenyl, 2-butenyl, 3-butenyl, 2-methyl-2-propenyl and the like;lower cyclo-alkyl groups of 3 to 7 carbon atoms optionally substitutedby lower alkyl groups such as cyclopropyl, cyclopentyl,2-methylcyclopentyl, cyclohexyl, 3-methyl-cyclohexyl and the like; lowercycloalkenyl groups of 3 to 7 carbon atoms optionally substituted bylower alkyl groups such as 3-cyclopentenyl, 1-methyl-3-cyclopentenyl and3-cyclohexenyl; lower alkyl or alkenyl groups substituted by lowercycloalkyl or cycloalkenyl groups such as cyclopropylmethyl,cyclopropylethyl, cyclopentylmethyl, cyclohexylmethyl,2-cyclohexenyl-methyl and 3-cyclopropyl-2-propenyl. The preferred lowerhydrocarbon groups are saturated. The lower alkyl and lower cycloalkylgroups, especially the lower alkyl groups, are particularly preferredlower hydrocarbon groups.

The term "aryl" denotes carbocyclic aromatic groups, preferably mono- orbicyclic groups, for example, phenyl and naphthyl groups, especiallyphenyl, which may be optionally substituted by one, two or threesubstituents selected from the group consisting of basic amino, loweralkyl, lower alkoxy, lower alkylthio, lower alkanoyl, loweralkoxycarbonyl, aryl (especially phenyl), halogen, trifluoromethyl,hydroxy, nitro and cyano. These groups are preferably unsubstituted orsubstituted by one, two or three substitutents from the group consistingof lower alkyl, lower alkoxy, lower alkylthio, halogen, nitro anddi(lower alkyl)amino.

The term "arylene" denotes carbocyclic aromatic groups with two freevalencies, preferably mono- or bicyclic groups, for example, phenyleneand naphthylene groups, especially 1,4- or 1,2-phenylene groups and, inparticular, 1,4-phenylene, which can be substituted by one or twosubstituents selected from the group consisting of lower alkyl, loweralkoxy, lower alkythio, lower alkanoyl, lower alkoxycarbonyl, aryl(especially phenyl), halogen, trifluoromethyl, hydroxy, nitro and cyano.They are preferably unsubstituted.

The term "heteroaryl" denotes heterocyclic aromatic groups, preferablymono- or bicyclic groups, especially 5- or 6-membered aromaticheterocycles which are optionally fused with a benzene ring and whichcan be optionally substituted by one, two or three substituents selectedfrom the group consisting of basic amino, lower alkyl, lower alkoxy,lower alkylthio, lower alkanoyl, lower alkoxycarbonyl, aryl (especiallyphenyl), halogen, trifluoromethyl, hydroxy, nitro and cyano. The5-membered aromatic heterocycles preferably contain as the hetero ringmember(s) an oxygen or sulfur atom or an imino group and optionally inaddition one or two nitrogen atoms. The 6-membered aromatic heterocyclespreferably contain as the ring member(s) one, two or three nitrogenatoms.

The term "heteroarylene" denotes heterocyclic aromatic groups with twofree valencies, preferably mono- or bicyclic groups, especially 5- and6-membered aromatic heterocycles with two free valencies, which areoptionally fused with a benzene ring and which can be substituted by oneor two substituents selected from the group consisting of lower alkyl,lower alkoxy, lower alkylthio, lower alkanoyl, lower alkoxycarbonyl,aryl (especially phenyl), halogen, trifluoromethyl, hydroxy, nitro andcyano.

The term "halogen" denotes fluorine, chlorine, bromine and iodine.

The term "basic amino group" or "basic amino" denotes unsubstituted ormono- or disubstituted amino groups having a basic character. The basicamino groups can be represented by the formula --NRR', whereinpreferably R is hydrogen or lower alkyl and R' is hydrogen or asaturated or partially unsaturated lower hydrocarbon group which isoptionally substituted by one or two lower alkoxy or hydroxy groups orby an amino, lower alkylamino, lower dialkylamino, oxo, loweralkoxycarbonyl or lower alkylenedioxy group or R and R' taken togetherwith the nitrogen atom are a 4- to 7-membered saturated N-heterocyclewhich is optionally substituted by one or two lower alkyl groups andwhich can contain as a ring member in place of a methylene group anoxygen or sulfur atom or the group >SO, >SO₂, >CO, >CH--Rf or >N--Rg inwhich Rf is hydroxy, lower alkanoyl, lower alkoxycarbonyl, carbamoyl,mono- or di(lower alkyl)carbamoyl or a saturated or partiallyunsaturated lower hydrocarbon group which is optionally attached via anoxygen atom and which is optionally substituted by one or two loweralkoxy or hydroxy groups, or by an amino, lower alkylamino, lowerdialkylamino, oxo, lower alkoxycarbonyl or lower alkylenedioxy group andRg is hydrogen, lower alkanoyl, lower alkoxycarbonyl, carbamoyl, mono-or di(lower alkyl)carbamoyl or a saturated or partially unsaturatedlower hydrocarbon group which is optionally substituted by one or twolower alkoxy or hydroxy groups or by an amino, lower alkylamino, lowerdialkylamino, oxo, lower alkoxycarbonyl or lower alkylenedioxy group.

Especially preferred basic amino groups characterized by the formula--NRR' are those in which R is hydrogen or lower alkyl and R' is asaturated lower hydrocarbon group or R and R' taken together with thenitrogen atom are a 4-, 5- or 6-membered saturated N-heterocycle whichis optionally substituted by hydroxy, lower alkoxy, lower hydroxyalkylor lower alkoxyalkyl or a 6-membered saturated N-heterocycle which isoptionally substituted by one or two lower alkyl groups and whichcontains in place of a methylene group an oxygen or sulfur atom or animino or lower alkylimino group.

Particularly preferred basic amino groups characterized by the formula--NRR' are those in which R and R' independently are lower alkyl ortaken together with the nitrogen atom are 1-pyrrolidinyl, 1-piperidinyl,4-morpholinyl, 2,6-dimethyl-4-morpholinyl, 4-thiomorpholinyl or4-methyl-1-piperazinyl.

If a compound of formula I contains more than one basic amino group,then the groups can be the same or different.

The term "leaving group" preferably denotes a halogen atom such aschlorine, bromine and iodine, lower alkylsulfonyloxy such asmethylsulfonyloxy and arylsulfonyloxy such as p-tolysulfonyloxy.

In a preferred embodiment, the invention relates to compounds of formulaI above in which R³ is lower alkylthio.

In a further preferred embodiment, the invention relates to compounds offormula I above in which R³ is the groups --(A)_(n) --Ra. Preferably, nis the integer 0 or the integer 1, whereby A preferably is vinylene. Ina preferred embodiment, Ra is an unsubstituted phenyl group or a phenylgroup substituted by one, two or three substituents from the groupconsisting of lower alkyl, lower alkoxy, lower alkylthio, halogen, nitroand di(lower alkyl)amino, whereby Ra is, in particular, an unsubstitutedphenyl group or phenyl groups mono-substituted by lower alkyl, loweralkoxy or halogen, such as phenyl, p-chlorophenyl, p-tolyl,m-methoxyphenyl and the like. In a still more preferred embodiment, Rais the group --NRR' in which R and R' independently are hydrogen orlower alkyl or taken together with the nitrogen atom are a 5- or6-membered saturated heterocycle which is optionally substituted by oneor two lower alkyl groups and which contains as the hetero atoms one ortwo nitrogen atoms or one nitrogen atom and one oxygen or sulfur atom.Preferably, R and R' independently are lower alkyl, especially methyl,or taken together with the nitrogen atom are 4-morpholinyl or1-piperidinyl.

The R⁵ preferably is hydrogen.

In a preferred embodiment, R⁴ is the group --N═CR⁶ --Q--NR¹ R².

In a further preferred embodiment, R⁴ is the group --CHRc--CO--Re inwhich Rc preferably is hydrogen and Re preferably is lower alkyl, loweralkoxy, an unsubstituted phenyl group or a phenyl group substituted byone, two or three substituents from the group consisting of lower alkyl,lower alkoxy, lower alkylthio, halogen, nitro and di(lower alkyl)amino.More particularly, Re is lower alkyl, especially t-butyl.

Preferably, Q is 1,4-phenylene optionally substituted by one or twosubstituents from the group consisting of lower alkyl and lower alkoxy.In an especially preferred embodiment, Q is 1,4-phenylene.

Preferably, R¹ and R² independently are lower alkyl. In an especiallypreferred embodiment, each one of R¹ and R² is methyl.

Preferably, R⁶ is hydrogen.

The imidazolium salts listed hereinafter are exemplary of the preferredcompounds of the class of compounds of characterized by formula I:

1,3-Bis[[p-(dimethylamino)benzylidene]amino]-2-[2-(dimethylamino)vinyl]imidazoliumchloride,

1,3-bis[[p-(dimethylamino)benzylidene]amino]-2-[(2-piperidinovinyl)imidazoliumchloride,

1,3-bis[[p-(dimethylamino)benzylidene]amino]-2-[(2-morpholinovinyl)imidazoliumchloride,

1,3-bis[[p-(dimethylamino)benzylidene]amino]-2-phenylimidazoliumchloride,

1,3-bis[[p-(dimethylamino)benzylidene]amino]-2-(p-chlorophenyl)imidazoliumchloride,

3-[[p-(dimethylamino)benzylidene[amino[-1-(pivaloylmethyl)-2-(p-tolyl)imidazoliumbromide;

3-[[p-(dimethylamino)benzylidene]amino]-1-(pivaloylmethyl)-2-(m-methoxyphenyl)imidazoliumbromide and the like.

The compounds of formula I and their pharmaceutically acceptable acidaddition salts can be prepared in accordance with the invention by

(a) reacting a compound of the formula ##STR4## wherein R³, R⁴, R⁵ andthe dotted line are as previously described and Ya⁻ is an anion, with acarbonyl compound of the formula

    R.sup.1 R.sup.2 N--Q--CO--R.sup.6                          IV

wherein R¹, R², R⁶ and Q are as previously described, or

(b) reacting a compound of the formula ##STR5## wherein R¹, R², R³, R⁵,R⁶ and Q are as previously described, with a compound of the formula

    R.sup.41 --X                                               VI

wherein R⁴¹ is a saturated or partially unsaturated lower hydrocarbongroup or the group --CHRcRd or --CHRc--CO--Re and X is a leaving group,and Rc, Rd and Re are as previously described, or

(c) condensing a compound of the formula ##STR6## wherein R¹, R², R⁴,R⁵, R⁶, Q, Ya⁻ and the dotted line are as previously described, with analdehyde of the general formula

    Ra--CHO                                                    VIII

wherein Ra is as previously described, or

(d) reacting a compound of the formula ##STR7## wherein R¹, R², R⁴, R⁵,R⁶, Q, Ya⁻ and the dotted line are as previously described, and R" islower alkyl, with ammonia or a primary or secondary basic amine,

(e) optionally replacing the anion denoted by Ya⁻ in a compound obtainedby a pharmaceutically acceptable anion and

(f) if desired, converting a compound of formula I obtained into apharmaceutically acceptable salt.

In several of the above processes, in accordance with the invention, itis necessary to block with a protecting group any reactive amino and/orhydroxyl groups in the starting materials. Such cases are readilyrecognizable by the person skilled in the art and the choice of suitableprotecting groups are also known to a person skilled in the art.

The reaction of amines with aldehydes or ketones in accordance withprocess variant (a) is a reaction which is known and which is familiarto any person skilled in the art. Suitable solvents are, for example,water, lower fatty acids such as acetic acid and propionic acid; loweralcohols such as methanol, ethanol, 1-propanol and 2-propanol; lowerfatty acid esters such as ethyl acetate, lower ethers such as diethylether, t-butyl methyl ether, ethylene glycol dimethyl ether,tetrahydrofuran and dioxane; halogenated lower hydrocarbons such asmethylene chloride, chloroform and ethylene chloride; aromatichydrocarbons such as benzene, toluene and xylene; acetonitrile;N,N-dimethylformamide and dimethyl sulfoxide. The reaction temperatureis not critical. The reaction can be carried out, for example, at atemperature in a range of about 0° C. up to the boiling temperature ofthe chosen solvent. However, the reaction is preferably carried out atroom temperature. In the reaction with the less reactive ketones offormula IV (R⁶ =lower alkyl), a condensation agent such astriethyloxonium tetrafluoro borate is preferably used.

Compounds of formula I in which R⁴ is a saturated or partiallyunsaturated lower hydrocarbon group or the group --CHRcRd or--CHRc--CO--Re can be prepared in accordance with process variant (b) byalkylating imidazole derivatives of formula V. This is also a reactionwhich is known and which is familiar to any person skilled in the art.Suitable solvents are, for example, halogenated lower hydrocarbons suchas methylene chloride, chloroform and ethylene chloride; open-chain orcyclic ethers such as diethyl ether, t-butyl methyl ether, ethyleneglycol dimethyl ether, tetrahydrofuran and dioxane; lower fatty acidesters such as ethyl acetate; lower alcohols such as methanol, ethanol,1-propanol and 2-propanol; aromatic hydrocarbons such as benzene,toluene and xylene; acetonitrile; N,N-dimethylformamide and dimethylsulfoxide. A lower alcohol such as 2-propanol or acetonitrile ispreferably used. The reaction temperature is not critical. For example,the reaction can be carried out at a temperature in a range of about 0°C. up to the boiling temperature of the solvent, preferably thetemperature is in a range of about room temperature to about 60° C.

Compounds of formula I in which R³ is the group --CH═CH--Ra can beprepared in accordance with process variant (c) by condensing a compoundof formula VII with an aldehyde of formula VIII. This is also a reactionwhich is known and which is familiar to any person skilled in the art.Insofar as Ra is aryl or heteroaryl, the reaction is preferably carriedout in the presence of a secondary amine, especially a cyclic amine suchas piperidine or morpholine. Suitable solvents are, for example, loweralcohols such as methanol, ethanol, 1-propanol and 2-propanol; aromatichydrocarbons such as benzene and toluene; open-chain and cyclic etherssuch as ethylene glycol dimethyl ether, tetrahydrofuran and dioxane;halogenated lower hydrocarbons such as methylene chloride;N,N-dimethylformamide and dimethyl sulfoxide. The reaction is preferablycarried out at the boiling temperature of the chosen solvent. In apreferred embodiment, the solvent used is a water-entrainer, for examplean aromatic hydrocarbon or a halogenated lower hydrocarbon, and thewater which is formed in the reaction is removed using a waterseparator.

Insofar as Ra is a basic amino group, the aldehyde of formula VIII ispreferably used in the form of a corresponding di(lower alkyl)acetal,whereby the previously mentioned solvents are also suitable for thepresent case. A lower alcohol such as 1-propanol; a halogenated lowerhydrocarbon such as methylene chloride; or dimethylformamide ispreferably used as the solvent. The reaction temperature is notcritical. The reaction can be carried out at a temperature in a range ofabout room temperature up to the boiling temperature of the chosensolvent. However, the reaction is preferably carried out at atemperature in a range of about room temperature up to about 100° C.

Compounds of formula I in which R³ is a basic amino group can beprepared in accordance with process variant (d) by reacting a compoundof formula Ib with ammonia or a primary or secondary basic amine. Thisis also a reaction which is known and which is familiar to any personskilled in the art. Suitable solvents are, for example, halogenatedlower hydrocarbons such as methylene chloride; open-chain and cyclicethers such as diethyl ether, t-butyl methyl ether, tetrahydrofuran anddioxane; N,N-dimethylformamide; acetonitrile and dimethyl sulfoxide.N,N-Dimethylformamide and acetonitrile are preferred solvents. Thereaction temperature is not critical and the reaction can be carriedout, for example, at a temperature from in a range of about 0° C. to theboiling temperature of the chosen solvent. However, the reaction ispreferably carried out at room temperature.

The anion denoted by Ya⁻ in a compound obtained can be replaced by apharmaceutically acceptable anion in accordance with process variant(e). This replacement reaction is also a reaction which is known andwhich is familiar to any person skilled in the art. Conventionalion-exchangers which are loaded with a pharmaceutically acceptable anionare preferably used.

Compounds of formula I can be converted into pharmaceutically acceptableacid addition salts in accordance with process variant (f). Such acidaddition salts can be prepared according to known methods and which arefamiliar to any person skilled in the art. There come intoconsideration, not only salts with inorganic acids, but also salts withorganic acids, for example hydrochlorides, hydrobromides, sulfates,nitrates, citrates, acetates, maleates, succinates, methanesulfonates,p-toluenesulfonates and the like.

The compounds of formula II which are used as starting materials can beprepared, for example, in accordance with Reaction Scheme I in which R³,R⁵, Ya⁻ and the dotted line are as previously described: ##STR8##

Compounds of formula II in which R³ is lower alkylthio can also beprepared, for example, in accordance with Reaction Scheme II in whichR⁵, R", Ya⁻ and the dotted line are as previously described and φ isphenyl: ##STR9##

Compounds of formula II in which R³ is the group --CH═CH--Ra can also beprepared, for example, in accordance with Reaction Scheme III in whichR⁵, Ra, Ya⁻, the dotted line and φ are as previously described:##STR10##

Compounds of formula II in which R³ is a basic amino group can also beprepared, for example, in accordance with Reaction Scheme IV in whichR⁵, Ya⁻, the dotted line and φ are as previously described and Ra" is abasic amino group: ##STR11##

The compounds of formula II in which R³ is the group --A'--Ra", A' islower alkylene and Ra" is a basic amino group can also be prepared, forexample, in accordance with Reaction Scheme V in which R⁵, Ra", A', φ,Ya⁻ and the dotted line are as previously described and X' is halogen:##STR12##

The compounds of formula III can be prepared in accordance with theforegoing Reaction Schemes I-V by using, in each case, as the startingmaterial in place of a compound of formula X, a corresponding compoundof the formula ##STR13## wherein Rh is hydrogen, methyl, the group--A'--OH or R³ and A', R³, R⁴ and R⁵ are as previously described.

The compounds of formula III in which R⁴ is a saturated or partiallyunsaturated lower hydrocarbon group or the group --CHRcRd or--CHRc--CO--Re can also be prepared, for example, in accordance with thefollowing Reaction Scheme VI in which R³, R⁴¹, R⁵, Ya⁻, φ and the dottedline are as previously described: ##STR14##

The compounds of formula III in which R⁴ is a saturated or partiallyunsaturated lower hydrocarbon group or the group --CHRcRd or--CHRc--CO--Re and R³ is the group --SR", --CH═CH--Ra, Ra" or --A'--Ra"can also be prepared by converting a compound of formula Xb, Xc or Xe'in accordance with the foregoing Reaction Scheme VI, in place ofcompound Xa, into the compound corresponding to formula XVIIa andfurther processing this in place of the compounds of formula XII, inaccordance with Reaction Schemes II, III, IV and V.

The reaction steps A-G referred to in the Reaction Schemes are explainedhereinafter in more detail. In each case the reactions are known and arefamiliar to any person skilled in the art.

Aa: This reaction step is an electrophilic amination with an aminatingagent such as O-(2,4-dinitrophenyl)-hydroxylamine,O-mesitylenesulfonylhydroxylamine or hydroxylamine O-sulfonic acid orits salts with inorganic bases. Preferably, the corresponding alkalimetal salts of hydroxylamine O-sulfonic acid, for example, the sodiumsalt, are used and the reaction is carried out in aqueous solution. Inthis case, there is generally obtained a mixture consisting of thediamine of formula II or XI and the monoamine of formula X. The twocompounds can be separated from each other according to known methodsand which are familiar to any person skilled in the art. The Exampleswhich follow contain detailed information concerning the separation ofthe mixtures obtained.

Ab: This reaction step is an electrophilic amination with an aminatingagent such as O-diphenylphosphinylhydroxylamine orO-mesitylenesulfonylhydroxylamine, whereby the starting material isconverted with a strong base into an alkali metal salt prior to thereaction with the aminating agent. Suitable bases are, for example,lower alkali metal alkoxides such as sodium methoxide and sodiumethoxide, and alkali metal hydrides such as sodium hydride. Suitablesolvents are, for example, N-methylpyrrolidone, N,N-dimethylformamide,lower alcohols, ethers such as tetrahydrofuran, diethylene glycoldimethyl ether, diethylene glycol diethyl ether and diethylene glycoldibutyl ether. The reaction temperature preferably lies in a range ofabout 0° C. to 100° C. The reaction is preferably carried out at roomtemperature.

Ac: This reaction step is an electrophilic amination with an aminatingagent such as O-diphenylphosphinylhydroxylamine orO-mesitylenesulfonylhydroxylamine. Suitable solvents are, for example,halogenated lower hydrocarbons such as chloroform, methylene chlorideand ethylene chloride; ethers such as diethyl ether and tetrahydrofuran;lower alcohols such as ethanol; acetonitrile; N,N-dimethylformamide;dimethyl sulfoxide; and mixtures thereof. The reaction temperature liesin a range of from about 0° C. to the boiling temperature of the chosensolvent. The reaction is preferably carried out at room temperature.

B: In this reaction step, the corresponding starting material isconverted into the corresponding aldimine with benzaldehyde. Suitablesolvents are, for example, lower fatty acids such as acetic acid andpropionic acid; lower alcohols such as methanol, ethanol and 2-propanol;acidic-aqueous media; halogenated lower hydrocarbons such as methylenechloride, chloroform and ethylene chloride; open-chain and cyclic etherssuch as diethyl ether, diisopropyl ether, t-butyl methyl ether, ethyleneglycol dimethyl ether, diethylene glycol diethyl ether, tetrahydrofuranand dioxane; acetonitrile; N,N-dimethylformamide and dimethyl sulfoxide.The reaction can be carried out of a temperature in the range of fromabout 0° C. up to the boiling temperature of the chosen solvent. Thereaction is preferably carried out at room temperature.

C: The desired thioxo group can be introduced, for example, by treatingthe starting material with elemental sulfur in the presence of atertiary amine and in a suitable solvent, for example, in pyridine. Thereaction can be carried out at a temperature in a range of from aboutroom temperature to the boiling temperature of the reaction mixture.

D: The desired alkylation can be carried out, for example, by treatingthe starting material with an alkylating agent such as a tri(loweralkyl)oxonium tetrafluoroborate, for example, with trimethyloxoniumtetrafluoroborate. Suitable solvents are, for example, halogenated lowerhydrocarbons such as methylene chloride. The reaction is preferablycarried out at room temperature.

E: This reaction step comprises the hydrolysis of an aldimine. In apreferred embodiment, the corresponding starting material is treatedwith an aqueous acid and the aromatic aldehyde obtained is removed bysteam distillation. Suitable acids are, for example, dilute hydrochloricacid and dilute hydrobromic acid and tetrafluoroboric acid.

F: In this reaction a compound of formula XIIc is condensed with analdehyde of formula VIII. When, Ra is aryl or heteroaryl, the reactionis preferably carried out in the presence of a secondary amine,especially a cyclic amine such as piperidine or morpholine. Suitablesolvents are, for example, lower alcohols such as methanol, ethanol,1-propanol and 2-propanol; aromatic hydrocarbons such as benzene andtoluene; open-chain and cyclic ethers such as ethylene glycol dimethylether, tetrahydrofuran and dioxane; halogenated lower hydrocarbons suchas methylene chloride; N,N-dimethylformamide and dimethyl sulfoxide. Thereaction is preferably carried out at the boiling temperature of thechosen solvent. In a preferred embodiment the solvent used is awater-entrainer, for example an aromatic hydrocarbon or a halogenatedlower hydrocarbon, and the water which is formed in the reaction isremoved with a water separator.

Where Ra is a basic amino group, the aldehyde of formula VIII ispreferably used in the form of a corresponding di(lower alkyl)acetal,whereby the previously mentioned solvents are also suitable in thepresent case. A lower alcohol such as 1-propanol; a halogenated lowerhydrocarbon such as methylene chloride; or dimethylformamide ispreferably used as the solvent. The reaction temperature is notcritical. The reaction can be carried out at a temperature in a range offrom about room temperature to the boiling temperature of the chosensolvent. However, the reaction is preferably carried out in a range ofabout room temperature up to about 100° C.

G: In this reaction step, a compound of formula XIVb is reacted withammonia or a primary or secondary basic amine. Suitable solvents are,for example, halogenated lower hydrocarbons such as methylene chloride;open-chain and cyclic ethers such as diethyl ether, t-butyl methylether, tetrahydrofuran and dioxane; N,N-dimethylformamide; acetonitrileand dimethyl sulfoxide. N,N-Dimethylformamide and acetonitrile arepreferred solvents. The reaction temperature is not critical and thereaction can be carried out, for example, at a temperature in a range offrom about 0° C. up the boiling temperature of the chosen solvent.However, the reaction is preferably carried out at room temperature.

H: In this reaction step, a compound of formula XIIe' is reacted with ahalogenating agent such as thionyl chloride and phosphorus oxychloride,whereby excess halogenating agent is preferably used as the solvent. Thereaction can be carried out at a temperature range of from about 0° C.to the boiling temperature of the reaction mixture.

I: In this reaction step, a compound of formula XIIe is reacted withammonia or a primary or secondary basic amine, wherein acetone orN,N-dimethylformamide is preferably used as the solvent. The reactioncan be carried out at a temperature range of from about room temperatureto the boiling temperature of the reaction mixture.

J: In this reaction step, the corresponding starting material is reactedwith a compound of formula VI above. Suitable solvents are, for example,halogenated lower hydrocarbons such as methylene chloride, chloroformand ethylene chloride; open-chain and cyclic ethers such as diethylether, diisopropyl ether, ethylene glycol dimethyl ether, diethyleneglycol diethyl ether, tetrahydrofuran and dioxane; acetonitrile andN,N-dimethylformamide. This reaction can be carried out at a temperaturerange of from about 0° C. to the boiling temperature of the chosensolvent.

The compounds of formula V which are used as starting materials can beprepared in analogy to process variant (a) or to reaction step Bdescribed above by reacting a compound of formula Xa with an aldehyde orketone of formula IV.

The compounds of formula VII which are used as starting materials andthe starting materials for their preparation can be prepared in analogyto process variants (a) and (b) or in analogy to the processes describedfor the preparation of the starting materials used in these processvariants.

The above-described compounds which are used as starting materials andtheir use for the preparation of therapeutically active substances offormula I, which have as a common structural feature a group of theformula ##STR15## wherein R³, R⁵ and Y⁻ have the above significance,also form part of the invention. These are the above-defined compoundsof formulas II, III and V.

As mentioned earlier, the compounds of formula I possess valuablepharmacological properties, which render the compounds of formula Iparticularly useful as antibacterial, antimycotic, protozoacidal and/oranthelmintic agents. By way of further exemplification, the compounds offormula I exhibit antiparasitic properties and are especially activeagainst parasitic protozoa and worms. Their activity against parasiticworms, especially against nematodes such as the filaria, is especiallypronounced. These pharmacological properties can be demonstrated bymeans of test methods which are known and which are familiar to anyperson skilled in the art.

The filaricidal activity of the compounds of formula I can bedetermined, for example, on cotton rats (Sigmodon hispidus) which havebeen infected with Litomosoides carinii. The infection with L. cariniiis transmitted by the blood-sucking mite Bdellonyssus bacoti in whichthe development of the microfilaria in infectious larvae takes place.The cotton rats are infected by exposing them to bites of infectedmites. After fourteen (14) weeks, the infected groups of 2-4 animals aretreated subcutaneously with the compound to be tested. Forty two (42)days after treatment with the compound to be tested, the experimentalanimals are dissected, and the adult filaria are removed from thepleural cavity. Living and dead or encapsulated worms are separated fromone another and weighed. The filaricidal activity is expressed as thepercentage proportion of dead macrofilaria per treatment group. The ED₉₀is then determined by means of Probit analysis using the values fromdifferent dosage groups. The ED₉₀ is that dosage at which 90% of theworms removed from the pleural cavity are dead. In the following Table,the results which were obtained in the previously described test withrepresentative members of the class of compound defined by formula I arecompiled. Moreover, the Table contains data concerning the acutetoxicity of some of the compounds of formula I in mg per kg obtainedafter single oral administration to mice.

                  TABLE                                                           ______________________________________                                                     ED.sub.90 in mg/kg                                                                        LD.sub.50 in mg/kg                                   Compound     s.c.        p.o.                                                 ______________________________________                                        A            1.0         312-625                                              B            2.0         --                                                   C            0.55        --                                                   D            <1.0        1250-2500                                            ______________________________________                                         Compound A =                                                                  1,3Bis[[p(dimethylamino)benzylideneamino2-[2(dimethylamino)vinyl]imidazol    um chloride.                                                                   Compound B =                                                                  1,3Bis[[p(dimethylamino)benzylideneamino2-(2-piperidinovinyl)imidazolium      chloride.                                                                     Compound C =                                                                  1,3Bis[[p(dimethylamino)benzylideneamino2-(2-morpholinovinyl)imidazolium      chloride.                                                                     Compound D = 1,3Bis[[p(dimethylamino)benzylideneamino2-phenylimidazolium      chloride.                                                                

The compounds of formula I can be used as medicaments, for example, inthe form of pharmaceutical preparations for enteral or parentaladministration. The compounds of formula I can be administered,perorally, for example, in the form of tablets, coated tablets, dragees,hard and soft gelatine capsules, solutions, emulsions or suspensions;rectally, for example, in the form of suppositories; or parenterally,for example, in the form of injection solutions.

The preparation of the pharmaceutical preparations can be carried in amanner which is familiar to any person skilled in the art by bringingthe substances in accordance with the invention, optionally incombination with other therapeutically valuable substances, into agalenical form together with suitable, non-toxic, inert, therapeuticallycompatible solid or liquid carrier materials and, if desired, the usualpharmaceutical adjuvants.

Suitable carrier materials include not only inorganic carrier materials,but also organic carrier materials. Thus, for tablets, coated tablets,dragees and hard gelatine capsules there can be used as carriermaterials, for example, lactose, maize starch or derivatives thereof,talc, stearic acid or its salts. Suitable carriers for soft gelatinecapsules are, for example, vegetable oils, waxes, fats and semi-solidand liquid polyols. Depending on the nature of the active substance, nocarriers are, however, required in the case of soft gelatine capsules.Suitable carrier materials for the preparation of solutions and syrupsare, for example, water, polyols, saccharose, invert sugar and glucose.Suitable carrier materials for injection solutions are, for example,water, alcohols, polyols, glycerine and vegetable oils. Suitable carriermaterials for suppositories are, for example, natural or hardened oils,waxes, fats and semi-liquid or liquid polyols.

As pharmaceutical adjuvants, the usual stabilizing, preserving, wettingand emulsifying agents, flavor-improving agents, salts for varying theosmotic pressure, buffer substances, solubilizers, coloring and coatingagents and antioxidants, can be used.

The dosage at which the compounds of formula I are administered can varywithin wide limits depending on the disease to be treated, the age andthe individual condition of the warm-blooded host requiring treatmentand on the mode of administration and will, of course, be adjusted tothe individual requirements in each particular case. For theprophylactic and therapeutic use of the compounds of formula in thetreatment of infectious diseases which are caused by bacteria, fungi orparasites, the compounds of formula I are administered to adult patientsat a daily dosage of about 0.01 g to about 4 g, especially from about0.05 g to about 2 g. Depending on the dosage, it is convenient toadminister the daily dosage in several unit doses.

The pharmaceutical preparations in accordance with the inventionconveniently contain from about 10-1000 mg, preferably 50-500 mg, of acompound of formula I in accordance with the invention.

The Examples which follow further, illustrate the invention. Alltemperatures are given in degrees Celsius.

EXAMPLE 1

(a) A solution, of 10 g of hydroxylamine O-sulfonic acid prepared at 0°,and 7.4 g of sodium hydrogen carbonate in 60 ml of water is addeddropwise to a solution of 7.26 g of 2-methylimidazole in 30 ml of water.The temperature thereby rises to 35°. After stirring for 16 hours, themixture is acidified with 26 ml of 2N hydrochloric acid. A solution of6.26 g of benzaldehyde in 20 ml of ether is added thereto, whereupon themixture is stirred for an additional 6 hours. The precipitated productis filtered and recrystallized from methanol/ether. There is obtained1,3-bis(benzylideneamino)-2-methylimidazolium benzaldoxime O-sulfonateof melting point 249°-250°. The acidic filtrate obtained is processed inaccordance with Example 2a.

(b) 19.2 g of 1,3-bis(benzylideneamino)-2-methylimidazolium benzaldoximeO-sulfonate in 100 ml of water and 70 ml of 2N hydrochloric acid aresubjected to a steam distillation until benzaldehyde no longer results.The mixture is evaporated and the residue is placed on a column loadedwith 200 ml of ion-exchanger Amberlite IRA 400 (chloride). The column iseluted with about 1 liter of water. The eluate is evaporated and thematerial obtained is recrystallized from ethanol/methylene chloride.There is obtained 1,3-diamino-2-methyl-imidazolium chloride of meltingpoint 225°-227°.

(c) 0.22 of 1,3-diamino-2-methylimidazolium chloride is dissolved in 5ml of glacial acetic acid, whereupon the solution is treated with asolution of 0.45 g of 4-dimethylaminobenzaldehyde in 5 ml of glacialacetic acid. After stirring for 2 hours, the yellow precipitate isremoved by filtration. After drying, there is obtained1,3-bis[[p-(dimethylamino)benzylidene]amino]-2-methylimidazoliumchloride of decomposition point 264°-266°. The mother liquor is treatedwith ether, to yield a second portion of the desired product. Thematerial obtained is recrystallized from hot water. There is obtained1,3-bis[[p-(dimethylamino)benzylidene]amino]2-methylimidazolium chlorideof decomposition point 270°.

(d) 0.82 g of1,3-bis[[p-(dimethylamino)-benzylidene]amino]-2-methylimidazoliumchloride is suspended in 30 ml of ethanol, whereupon the suspension istreated with 0.3 g of 4-dimethylaminobenzaldehyde and 0.17 g ofpiperidine and heated to boiling under reflux. A deep red solutionresults. After 20 hours it is left to cool. The precipitated product isremoved by filtration and re-precipitated from methylene chloride/ether.After recrystallization from toluene there is obtained1.3-bis[[p-(dimethyl-amino)benzylidene]amino]-2-[p-(dimethylamino)styryl]imidazoliumchloride as a red solid of melting point 238°-240°.

EXAMPLE 2

(a) The acidic filtrate from Example 1a is extracted three times with 15ml of ether each time. The aqueous phase is neutralized with 9 ml of 4Nsodium hydroxide solution while cooling. The precipitate is removed byfiltration and re-precipitated from methanol/ether. There is obtained1-(benzylideneamino)-2-methylimidazole of melting point 122°-124°.

(b) 0.92 g of 1-(benzylideneamino)-2-methylimidazole is dissolved in 10ml of absolute dichloromethane and then treated with 0.74 g oftrimethyloxonium tetrafluoroborate. The mixture is stirred at roomtemperature overnight and the resulting precipitate is filtered undersuction and washed twice with dichloromethane. After reprecipitationfrom acetonitrile/diethyl ether, there is obtained colorless1-(benzylideneamino)-2,3-dimethylimidazolium tetrafluoroborate of m.p.213°-216°.

(c) 0.86 g of 1-benzylideneamino-2,3-dimethylimidazoliumtetrafluoroborate is suspended in 30 ml of water. The suspension istreated with 1 ml of 50 percent tetrafluoroboric acid andsteam-distilled until benzaldehyde no longer passes over. The colorlessacidic solution is then treated with 0.45 g ofp-(dimethylamino)benzaldehyde and stirred at room temperature for 3hours. The resulting orange-yellow precipitate is removed by filtrationunder suction, washed three times with water and three times withdiethyl ether and recrystallized from methanol/ethanol. There isobtained 1-[[p-(dimethylamino)benzylidene[amino[-2,3-dimethylimidazoliumtetrafluoroborate in the form of yellow needles with a melting point of248°-251°.

(d) 0.66 g of1-[[p-(dimethylamino)benzylidene]-amino]-2,3-dimethylimidazoliumtetrafluoroborate, 0.45 g of p-(dimethylamino)benzaldehyde and 0.34 g ofpiperidine are suspended in 30 ml of toluene, whereupon the suspensionis heated to boiling under reflux for about 70 hours on a waterseparator filled with toluene which contains 5% piperidine. Theprecipitated material is removed by filtration under suction, washedwith toluene, twice with diethyl ether and twice with water andrecrystallized from methanol. There is obtained colorless1-[[p-(dimethylamino)benzylidene]amino]-2-[p-(dimethylamino)styryl]-3-methylimidazoliumtetrafluoroborate of melting point 235°-238°.

EXAMPLE 3

(a) A solution of 1-(benzylideneamino)-2-methylimidazole in 1.5Nhydrochloric acid is subjected to a steam distillation untilbenzaldehyde no longer results. The mixture is evaporated and theproduct obtained in recrystallized from ethanol/ether. There is obtained1-amino-2-methylimidazole hydrochloride of melting point 124°.

(b) 1.3 g of 1-amino-2-methylimidazole hydrochloride and 2.2 g ofp-(dimethylamino)benzaldehyde are stirred at room temperature for 16hours in 100 ml of glacial acetic acid. The mixture is evaporated,whereupon the residue is treated four times with ethanol and againevaporated each time. The crystalline residue is washed with ether andthen treated with saturated sodium hydrogen carbonate solution. Themixture is extracted with methylene chloride, the extract is dried oversodium sulfate and evaporated, and the material obtained isrecrystallized from methylene chloride/petroleum ether. There isobtained 1-[[p-(dimethylamino)benzylidene]amino]-2-methylimidazole ofmelting point 166°-167°.

(c) 1.37 g of 1-[[p-(dimethylamino)benzylidene]-amino]-2-methylimidazoleare dissolved in 15 ml of absolute dimethylformamide. After the additionof 1.57 g of 3,4,5-trimethoxybenzyl bromide the mixture is stirred atroom temperature overnight. After cooling the reaction mixture in anice-bath, the resulting percipicate is removed by filtration undersuction, washed twice with ice-cold dimethylformamide and three timeswith diethyl ether and recrystallized from acetonitrile. There isobtained pale yellow1-[[p-(dimethylamino)benzylidene]-amino]-3-(3,4,5-trimethoxy)benzyl-2-methylimidazoliumbromide of melting point 238°-241°.

(d) 1.96 g of1-[[p-(dimethylamino)benzylidene]-amino]-3-(3,4,5-trimethoxy)benzyl-2-methylimidazoliumbromide, 0.9 g of p-(dimethylamino)benzaldehyde and 0.7 g of piperidineare suspended in 50 ml of toluene, whereupon the suspension is heated toboiling under reflux for about 60 hours on a water separator (filledwith toluene which contains 5% piperidine). The precipitated material isremoved by filtration under suction, washed with toluene, twice withdiethyl ether and thereafter three times with water and thenrecrystallized from ethanol and methanol. There is obtained orangecolored 1-[[p-(dimethylamino)benzylidene]amino]-2-[p-(dimethylamino)styryl]-3-(3,4,5-trimethoxybenzyl)imidazoliumbromide of melting point 253°-256° (decomposition).

EXAMPLE 4

(a) 680 mg of imidazole are suspended in a mixture of 4 ml of absoluteN-methyl-2-pyrrolidone and 1 ml of absolute tetrahydrofuran. Thesuspension is cooled to -40°. While stirring, there is slowly addeddropwise thereto within 30 minutes a solution of 4.8 g of0-(2,4-dinitrophenyl) hydroxylamine in 8 ml of absoluteN-methyl-2-pyrrolidone. The reaction mixture is left to stand at 20° for18 hours, treated with 25 ml of water and 12 ml of 2N hydrochloric acidand extracted five times with 20 ml of ether each time. The acidicsolution is stirred with active carbon for 15 minutes and there uponfiltered. After the addition of 3 ml of benzaldehyde, 5 ml of 2Nhydrochloric acid and 30 ml of ether the mixture is stirred for threehours while cooling with ice. The separated precipitate is removed byfiltration and washed twice with water and once with ether. Thethus-obtained crude product is re-precipitated from methanol/ether.There is obtained 1,3-bis(benzylideneamino)imidazolium chloride ofmelting point 193°-196°.

(b) 3.11 g of 1,3-bis(benzylideneamino)imidazolium chloride, 0.32 g ofsulfur and 1.01 g of triethylamine are suspended in 20 ml of absolutepyridine, whereupon the mixture is stirred at room temperature for 15minutes. The reaction mixture is subsequently heated to boiling underreflux for a half hour. After cooling to room temperature the mixture istreated with 100 ml of water. The resulting precipitate is removed byfiltration under suction and washed three times with water and threetimes with ethanol. There is obtained pale yellow1,3-bis(benzylideneamino)-1,3-dihydro-2H-imidazole-2-thione of meltingpoint 215°-218°.

(c) 3.06 g of1,3-bis(benzylideneamino)-1,3-dihydro-2H-imidazole-2-thione in 100 ml ofabsolute dichloromethane are treated with 1.47 g of trimethyloxoniumtetrafluoroborate, the mixture is stirred at room temperature for 3hours and the resulting precipitate is removed by filtration undersuction. From the filtrate, there is precipitated by the addition ofdiethyl ether an additional portion of the desired product which,together with the first portion, is washed once with water, once withcold methanol and three times with diethyl ether and subsequentlyre-precipitated from acetonitrile/diethyl ether. There is obtainedcolorless 1,3-bis(benzylideneamino)-2-(methylthio)imidazoliumtetrafluoroborate of melting point 215°-220° (decomposition).

(d) 4.47 g of 1,3-bis(benzylideneamino)-2-(methylthio) imidazoliumtetrafluoroborate are suspended in 100 ml of water. The suspension istreated with 3.5 ml of 50 percent tetrafluoroboric acid andsteam-distilled until benzaldehyde no longer evolves. The colorless,acidic solution, cooled to room temperature, is treated with 2.98 g ofp-dimethylaminobenzaldehyde and stirred at room temperature for 3 hours.The resulting yellow precipitate is removed by filtration under suction,washed three times with water, three times with ethanol and twice withdiethyl ether and subsequently re-precipitated from acetonitrile/diethylether. After recrystallization from ethanol, there is obtained1,3-bis[[p-(dimethylamino)-benzylidene]amino]-2-(methylthio) imidazoliumtetrafluoroborate as a yellow solid of melting point 250°-253°(decomposition).

EXAMPLE 5

Gaseous dimethylamine is passed through a mixture of 2.47 g of1,3-bis[[p-(dimethylamino)benzylidene]amino]-2(methylthio)imidazoliumtetrafluoroborate and 30 ml of absolute dimethylformamide until a weightincrease of 0.4 g (corresponding to 1.8 equivalents) is achieved and themixture is subsequently stirred at room temperature overnight. From theresulting reddish solution, there is obtained by the addition of diethylether a crystalline precipitate which is removed by filtration undersuction and washed twice with water and ethanol each time. Afterre-precipitation from dimethylformamide/diethyl ether, there is obtained1,3-bis[[p-(dimethylamino)benzylidene]amino]-2-(dimethylamino)imidazoliumtetrafluoroborate as a yellow solid of melting point 248°-252°(decomposition).

EXAMPLE 6

(a) 1.45 g of absolute morpholine are added under an argon atmosphere to4.1 g of 1,3-bis-(benzylideneamino)-2-(methylthio)imidazoliumtetrafluoroborate in 15 ml of absolute dimethylformamide, whereby theevolution of methyl mercaptan occurs immediately and a yellow-orangesolution results. The solution is stirred at room temperature until thecleavage of methyl mercaptan is complete (about 12 hours). Then thesolution is treated with 120 ml of diethyl ether and the resulting,slightly yellowish precipitate is removed by filtration under suction.The precipitate is washed five times with diethyl ether, and twice witha small amount of cold ethanol and re-precipitated fromacetonitrile/diethyl ether. There is obtained colorless1,3-bis(benzylideneamino)-2-morpholinoimidazolium tetrafluoroborate ofmelting point 242°-245° (decomposition).

(b) 2.24 g of 1,3-bis(benzylideneamino)-2-morpholinoimidazoliumtetrafluoroborate are suspended in water, whereupon the suspension istreated with 2 ml of 50 percent tetrafluoroboric acid andsteam-distilled until benzaldehyde no longer evolves. The colorless,acidic solution obtained is treated with 1.5 g ofp-(dimethylamino)benzaldehyde and stirred at room temperature for 3hours. The resulting orange-yellow precipitate is removed by filtrationunder suction, washed three times with water, three times with ethanoland three times with diethyl ether and subsequently re-precipitated fromdimethylformamide/diethyl ether. There is obtained yellow1,3-bis[[p-(dimethylamino)benzylidene]amino]-2-morpholinoimidazoliumtetrafluoroborate of melting point 275°-280° (decomposition).

EXAMPLE 7

2.47 g of1,3-bis[[p-(dimethylamino)benzylidene]amino]-2-(methylthio)imidazoliumtetrafluoroborate are suspended in 50 ml of absolute acetonitrile,whereupon the suspension is treated with 7.8 g of absolute2-amino-5-(diethylamino)pentane. The mixture is stirred at roomtemperature under an argon atmosphere for about 24 hours. The insolubleconstituents are removed by filtration and the filtrate is treated with450 ml of diethyl ether. The pale yellow precipitate obtained is removedby filtration under suction, washed three times with diethyl ether andrecrystallized from methanol/diethyl ether. There is obtained paleyellow 1,3-bis[[p-(dimethylamino)benzylidene]amino]-2-[[4-(diethylamino)-1-methylbutyl]amino]imidazoliumtetrafluoroborate of melting point 187°-191° (decomposition).

EXAMPLE 8

0.99 g of1,3-bis[[p-(dimethylamino)benzylidene]amino]-2-(methylthio)imidazoliumtetrafluoroborate is dissolved in 15 ml of absolute dimethylformamide.Dry ammonia is conducted into the reaction solution at room temperaturewhile stirring until the cleavage of methyl mercaptan is complete. Thesolution is treated with diethyl ether. The precipitate obtained iswashed twice with water and twice with cold methanol and re-precipitatedfrom dimethylformamide/diethyl ether. There is obtained yellow2-amino-1,3-bis[[p-(dimethylamino)benzylidene]amino]imidazoliumtetrafluoroborate with a decomposition point >260°.

EXAMPLE 9

(a) 0.18 g of sodium hydride (55 percent dispersion in oil) is washedwith tetrahydrofuran. A solution of 0.34 g of2-(4-methoxyphenyl)-imidazole in 8.3 ml of N-methylpyrrolidone is addeddropwise while stirring at 0°. As soon as hydrogen no longer forms themixture is warmed to room temperature. 0.46 g of O-diphenylphosphinylhydroxylamine is added in three portions. Afterstirring at room temperature for 18 hours, 8 ml of water are added. Themixture is stirred for an additional 1 hour and extracted six times with20 ml of dichloromethane each time. The extracts are dried over sodiumsulfate and evaporated, whereby the N-methyl-pyrrolidone is removed in ahigh vacuum. The crude product is chromatographed on 5 g of silica gelwhile eluting with chloroform/ethanol. There is obtained1-amino-2-(4-methoxyphenyl)imidazole as a dark colored oil.

(b) 0.1 g of 1-amino-2-(4-methoxyphenyl)imidazole is dissolved in 10 mlof dichloromethane. The solution is treated portionwise during 8 dayswith 0.29 g of O-diphenylphosphinylhydroxylamine, evaporated and theresidue is suspended in 10 ml of water. The difficulty solublediphenylphosphinic acid is removed by filtration and the filtrate isplaced on a column loaded with Amberlite IRA 400 (chloride), whereuponthe column is eluted with water. There is obtained1,3-diamino-2-(4-methoxyphenyl)imidazolium chloride.

(c) 131 mg of 4-(dimethylamino)benzaldehyde are added to a solution of90 mg of 1,3-diamino-2-(4-methoxyphenyl) imidazolium chloride in 2 ml ofglacial acetic acid. After stirring at room temperature for 48 hours,the dark yellow solution is evaporated. The residue is placed on acolumn loaded with 8 g of silica gel, whereupon the product is elutedwith dichloromethane/ethanol (9:1) and recrystallized fromethanol/ether. There is obtained1,3-bis[[p-(dimethylamino)benzylidene]amino]-2-(p-methoxyphenyl)imidazoliumchloride of melting point 250°.

EXAMPLE 10

(a) 3.55 g of sodium hydride (55 percent dispersion in oil) are washedwith tetrahydrofuran. A solution of 6.5 g of2-(4-methoxyphenyl)-imidazole in 153 ml of N-methylpyrrolidone is addeddropwise thereto at 0°. As soon as hydrogen no longer forms a total of8.8 g of O-diphenylphosphinylhydroxylamine are added portionwise theretoat room temperature. After stirring for 18 hours, the mixture is treatedwith 150 ml of water, acidified with 80 ml of 2N hydrochloric acid,stirred at 0° for an additional 1 hour and the precipitateddiphenylphosphinic acid is removed by filtration. Then, 3.85 ml ofbenzaldehyde are added to the acidic dark red filtrate and the mixtureis stirred for about 20 hours. The dark solution is washed twice with120 ml of ether each time and adjusted to pH 14 by the addition of 20 mlof 4N sodium hydroxide solution while cooling with ice. The mixture isextracted five times with 150 ml of dichloromethane each time. Theextract is dried over sodium sulfate and evaporated, whereby theN-methylpyrrolidone is removed in a high vacuum. The residue is placedon a column loaded with 200 g of silica gel and the product is elutedwith dichloromethane/ethanol (98:2) and then crystallized from ethanol.There is obtained 1-(benzylideneamino)-2-(p-methoxyphenyl)imidazole ofmelting point 155°.

(b) 3.73 g of 1-bromo-3,3-dimethyl-2-butanone are added to a solution of4.6 g of 1-(benzylideneamino)-2-(p-methoxyphenyl)imidazole in 250 ml ofabsolute acetonitrile. After stirring at 60° for 24 hours, the solutionis evaporated and the residue is crystallized from ethanol/ether. Thereis obtained1-(benzylideneamino)-2-(p-methoxyphenyl)-3-(pivaloylmethyl)imidazoliumbromide of melting point 244°.

(c) 5.0 g of1-(benzylideneamino)-2-(p-methoxyphenyl)-3-(pivaloylmethyl)imidazoliumbromide are suspended in 300 ml of water. The suspension is then treatedwith 10 ml of 48 percent hydrobromic acid. The suspension is nowsubjected to a steam distillation until benzaldehyde no longer results.The solution is evaporated. The residue is treated with ethanol and thesolvent is removed by distillation. There is obtained1-amino-2-(p-methoxyphenyl)-3-(pivaloylmethyl)imidazolium bromide as anoil.

(d) 1.50 g of p-(dimethylamino)benzaldehyde are added to a solution of3.7 g of 1-amino-2-(p-methoxyphenyl)-3-(pivaloylmethyl)imidazoliumbromide in 25 ml of glacial acetic acid. The mixture is stirred at roomtemperature for 15 hours. Then, 20 ml of ether are added thereto and,after an additional 3 hours, the product is removed by filtration. Afterrecrystallization from ethanol/ether, there is obtained1-[[p-(dimethylamino)benzylidene]amino]-2-(p-methoxyphenyl)-3-(pivaloylmethyl)imidazoliumbromide of melting point 241°.

EXAMPLE 11

(a) 9.0 g of sodium hydride (55 percent dispersion in oil) are suspendedin 600 ml of absolute tetrahydrofuran. 8.5 g of2-(p-methoxyphenyl)imidazole are added thereto within 5 minutes. Themixture is stirred until hydrogen is no longer liberated (1 hour). Then,34.5 g of O-diphenylphosphinylhydroxylamine are added portionwisethereto at 10° and the mixture is stirred at 10° for an additional 40minutes and then at room temperature for 18 hours. Saturated sodiumchloride solution is added thereto at 5° and the mixture is subsequentlyextracted with methylene chloride/methanol (99.5:0.5). The extract isdried over sodium sulfate and evaporated. There is obtained1-amino-2-(p-methoxyphenyl)imidazole as a brown oil.

(b) 9 g of 1-amino-2-(p-methoxyphenyl)imidazole are dissolved in 300 mlof glacial acetic acid, whereupon the solution is treated with 21.3 g ofp-(dimethylamino) benzaldehyde. After 24 hours, the mixture isevaporated and the residue is placed on a column loaded with 300 g ofsilica gel. The product is eluted with dichloro-methane/methanol (95:5).The dark eluate is treated with active carbon and evaporated. Theproduct is crystallized twice from methylene chloride/petroleum ether.There is obtained1-[[p-(dimethylamino)benzylidene]amino]-2-p-methoxyphenyl)imidazoliumacetate of melting point 93°. The resulting salt is treated with aqueoussodium bicarbonate solution and extracted with dichloromethane. Theextract is dried over sodium sulfate and evaporated. The product iscrystallized from petroleum ether. There is obtained1-[[p-(dimethylamino)benzylidene]amino]-2-(p-methoxyphenyl)imidazole ofmelting point 108°.

In an analogous manner:

From 2-(p-tolyl)imidazole, there is obtained1-[[p-(dimethylamino)benzylidene]amino]-2-(p-tolyl)imidazole of meltingpoint 127°-128° and

from 2-[(p-methylthio)phenyl]imidazole there is obtained1-[[p-(dimethylamino)benzylidene]amino]-2-[p-(methylthio)phenyl]imidazoleof melting point 147°.

(c) In analogy to Example 11b), from1-amino-2-(p-methoxyphenyl)imidazole and4-(dimethylamino)-3,5-dimethoxybenzaldehyde, there is obtained1-[[4-(dimethylamino)-3,5-dimethoxybenzylidene]amino]-2-(p-methoxyphenyl)imidazoleof melting point 118°-119° (ether/petroleum ether).

(d) 0.45 g of sodium hydride (55 percent dispersion in oil) is washedwith absolute tetrahydrofuran. A solution of 1.02 g of2-(3,4-dimethoxyphenyl)imidazole in 50 ml of N-methylpyrrolidone is thenadded dropwise thereto. The mixture is stirred at room temperature for20 minutes. 2.33 g of O-diphenylphosphinylhydroxylamine are addedthereto at 0° and the mixture is shaken. After standing for 24 hours,water is added thereto and the mixture is extracted with methylenechloride. The extract is dried over sodium sulfate and evaporated. Theresidual oil (1-amino-2-(3,4-dimethoxyphenyl)imidazole) is dissolved in20 ml of glacial acetic acid. Then. 1.49 g ofp-(dimethylamino)benzaldehyde are added thereto. The mixture is left tostand at room temperature for 2 days and evaporated. The crude productis placed on a column loaded with 100 g of silica gel. The product iseluted with methylene chloride/methanol (19:1). The eluate is treatedwith sodium bicarbonate solution and extracted with methylene chloride.The extract is dried over sodium sulfate and evaporated. Aftercrystallization from ether/petroleum ether, there is obtained1-[[p-(dimethylamino)benzylidene]amino]-2-(3,4-dimethoxyphenyl)imidazoleof melting point 149°.

In an analogous manner:

From 2-phenylimidazole, there is obtained1-[[p-(dimethylamino)benzylidene]amino]-2-phenylimidazole of meltingpoint 137°;

from 2-(p-ethoxyphenyl)imidazole, there is obtained1-[[p-(dimethylamino)benzylidene]amino]-2-(pethoxyphenyl)imidazole ofmelting point 168°-169°;

from 2-(m-methoxyphenyl)imidazole, there is obtained1-[[p-(dimethylamino)benzylidene]amino]-2-(m-methoxyphenyl)imidazole ofmelting point 131°-133° (methylene chloride/petroleum ether);

from 2-(3,4,5-trimethoxyphenyl)imidazole, there is obtained1-[[p-(dimethylamino)benzylidene]amino]-2-(3,4,5-trimethoxyphenyl)imidazoleof melting point 163° (ethanol) and

from 2-(p-nitrophenyl)imidazole, there is obtained1-[[p-(dimethylamino)benzylidene]amino]-2-p-nitrophenyl)imidazole ofmelting point 200° (ethanol/ether).

(e) A solution of 160 mg of1-[[p-(dimethylamino)benzylidene]amino]-2-(p-methoxyphenyl)imidazole and400 mg of 1-bromo-3,3-dimethyl-2-butanone in 3 ml of acetonitrile isstirred at 60° for 20 hours. The product is removed by filtration andwashed with ether. There is obtained1-[[p-(dimethylamino)benzylidene]amino]-2-(p-methoxyphenyl)-3-(pivaloylmethyl)imidazoliumbromide of melting point 262°.

In an analogous manner:

(f) From 1-[[p-(dimethylamino)benzylidene]amino]-2-phenylimidazole and1-bromo-3,3-dimethyl-2-butanone, there is obtained after 2 days at 60°,3-[[p-(dimethylamino)benzylidene]amino]-2-phenyl-1-(pivaloylmethyl)imidazoliumbromide of melting point 245°;

(g) from 1-[[p-(dimethylamino)benzylidene]amino]-2-(p-tolyl)imidazoleand 1-bromo-3,3-dimethyl-2-butanone, there is obtained after 20 hours at60°,3-[[p-(dimethylamino)benzylidene]amino]-1-(pivaloylmethyl)-2-(p-tolyl)imidazoliumbromide of melting point 260°;

(h) from1-[[p-(dimethylamino)benzylidene]amino]-2-(3,4-dimethoxyphenyl)imidazoleand 1-bromo-3,3-dimethyl-2-butanone, there is obtained after 20 hours at60°3-[[p-(dimethylamino)benzylidene]amino]-2-(3,4-dimethoxyphenyl)-1-(pivaloylmethyl)imidazoliumbromide of melting point 270°-271°;

(i) from1-[[p-(dimethylamino)benzylidene]amino]-2-[p-(methylthio)phenyl]imidazoleand 1-bromo-3,3-dimethyl-2-butanone, there is obtained after 4 days at60°,3-[[p-(di-methylamino)benzylidene]amino]-2-[p-(methylthio)phenyl]-1-(pivaloylmethyl)imidazoliumbromide of melting point 255°;

(j) from1-[[p-(dimethylamino)benzylidene]amino]-2-(p-ethoxyphenyl)imidazole and1-bromo-3,3-dimethyl-2-butanone, there is obtained after 4 days at 60°,3-[[p-(dimethylamino)benzylidene]amino]-2-(p-ethoxyphenyl)-1-(pivaloylmethyl)imidazolium bromide of melting point 242°;

(k) from1-[[p-(dimethylamino)benzylidene]amino]-2-(3,4,5-trimethoxyphenyl)imidazoleand 1-bromo-3,3-dimethyl-2-butanone, there is obtained3-[[p-(dimethylamino)benzylidene]amino]-2-(3,4,5trimethoxphenyl)-1-(pivaloylmethyl)imidazoliumbromide of melting point 224° (ethanol/ether);

(l) from1-[[p-(dimethylamino)benzylidene]amino]-2-(m-methoxyphenyl)imidazole and1-bromo-3,3-dimethyl-2-butanone, there is obtained3-[[p-(dimethylamino)benzylidene]amino]-2-(m-methoxyphenyl)-1-(pivaloylmethyl)imidazoliumbromide of melting point 238° (methylene chloride/methanol/petroleumether; decomposition);

(m) from1-[[p-(dimethylamino)benzylidene]amino]-2-(p-nitrophenyl)imidazole and1-bromo-3,3-dimethyl-2-butanone, there is obtained3-[[p-(dimethylamino)benzylidene]amino]-2-(p-nitrophenyl)-1-(pivaloylmethyl)imidazoliumbromide of melting point 258° (ethanol/ether/hexane) and

(n) from1-[[4-(dimethylamino)-3,5-dimethoxybenzylidene]amino]-2-(p-methoxyphenyl)imidazoleand 1-bromo-3,3-dimethyl-2-butanone, there is obtained after 15 days atroom temperature3-[[4-(dimethylamino)-3,5-dimethoxybenzylidene]amino]-2-(p-methoxyphenyl)-1-(pivaloylmethyl)imidazoliumbromide of melting point 218°-220° (acetonitrile/ether).

EXAMPLE 12

(a) 0.60 g of p-(dimethylamino)phenacyl bromide is added to a solutionof 0.80 g of1-[[p-(dimethylamino)benzylidene]amino]-2-(p-methoxyphenyl)-imidazole in80 ml of acetonitrile. After stirring at room temperature for 3 days,the product is removed by filtration and washed with ether. There isobtained3-[[p-(dimethylamino)benzylidene]amino]-1-[p-(dimethylamino)phenacyl]-2-(p-methoxyphenyl)imidazoliumbromide of melting point 234°.

(b) In an analogous manner, from1-[[p-(dimethylamino)benzylidene]amino]-2-(3,4,5-trimethoxyphenyl)imidazole,there is obtained after 2 days at 50° in acetonitrile3-[[p-(dimethylamino)benzylidene]amino]-1-[p-(dimethylamino)phenacyl]-2-(3,4,5-trimethoxyphenyl)imidazoliumbromide of melting point 232° (ethanol/ether).

EXAMPLE 13

0.92 g of p-methoxyphenacyl bromide is added to a solution of 0.32 g of1-[[p-(dimethylamino)-benzylidene]amino]-2-(p-methoxyphenyl)imidazole in20 ml of 2-propanol. After stirring for 3 days with the exclusion oflight, the mixture is evaporated. The residue is placed on a columnloaded with 20 g of silica gel. The product is eluted with methylenechloride/methanol (9:1). After crystallization from ethanol/ether, thereis obtained3-[[p-(dimethylamino)benzylidene]amino]-2-(p-methoxyphenyl)-1-(p-methoxyphenacyl)imidazoliumbromide of melting point 188°-191°.

EXAMPLE 14

(a) 0.93 g of p-chlorophenacyl bromide is added to a solution of 0.64 gof 1-[[p-(dimethylamino)benzylidene]amino]-2-(p-methoxyphenyl)imidazolein 20 ml of acetonitrile. After stirring at 60° for 6 hours, the mixtureis left to stand for 16 hours and the product is removed by filtrationand washed with ether. There is obtained1-(p-chlorophenacyl)-3-[[p-(dimethylamino)benzylidene]amino]-2-(p-methoxyphenyl)imidazoliumbromide of melting point 242°.

In an analogous manner, from1-[[p-(dimethylamino)benzylidene]amino]-2-(p-methoxyphenyl)imidazoleand:

(b) p-nitrophenacyl bromide, there is obtained after 3 days at roomtemperature,3-[[p-(dimethylamino)benzylidene]-amino]-2-(p-methoxyphenyl)-1-(p-nitrophenacyl)imidazoliumbromide of melting point 232°;

(c) ethyl 2-bromoacetate, there is obtained after 2 days at 50°,1-[[p-(dimethylamino)benzylidene]amino]-3-((ethoxycarbonyl)methyl]-2-(p-methoxyphenyl)imidazoliumbromide of melting point 165°-167°;

(d) 3,4,5-trimethoxybenzyl chloride, there is obtained after 2 days at60°,3-[[p-(dimethylamino)benzylidene]amino]-2-(p-methoxyphenyl)-1-(3,4,5-trimethoxybenzyl)imidazoliumchloride of melting point 227°-228° (ethanol/ether);

(e) t-butyl 2-bromoacetate, there is obtained after 2 days at roomtemperature,1-[(t-butoxycarbonyl)methyl]-3-[[p-(dimethylamino)benzylidene]amino]-2-(p-methoxyphenyl)imidazoliumbromide of melting point 203° (acetonitrile).

EXAMPLE 15

(a) 2.05 g of1,3-bis[[p-(dimethylamino)benzylidene]amino]-2-methylimidazoliumchloride and 7.35 g of N,N-dimethylformamide diethyl acetal are stirredat 100° for 45 minutes in 150 ml of 1-propanol. The product isprecipitated by the addition of ether. The precipitate is crystallizedfrom dichloromethane/methanol and recrystallized from ethanol. There isobtained1,3-bis[[p-(dimethylamino)benzylidene]amino]-2-[2-(dimethylamino)vinyl]imidazoliumchloride of melting point 246°-248°.

In an analogous manner, from1,3-bis[[p-(dimethylamino)benzylidene]amino]-2-methylimidazoliumchloride and:

(b) Tetrahydro-4H-1,4-thiazine-4-carboxaldehyde diethyl acetal, there isobtained after 7 days at 55° in dimethylformamide,1,3-bis[[p-(dimethylamino)benzylidene]amino]-2-(tetrahydro-4H-1,4-thiazin-4-yl)vinyl]imidazoliumchloride of melting point 247° (decomposition);

(c) cis-2,6-dimethylmorpholine-4-carboxaldehyde diethyl acetal, there isobtained after 6 days at 50° in dimethylformamide,1,3-bis[[p-(dimethylamino)benzylidene]amino]-2-[2-(cis-2,6-dimethylmorpholino)vinyl]imidazoliumchloride of melting point 251° (decomposition);

(d) pyrrolidine-1-carboxaldehyde diethyl acetal there is obtained after24 hours at reflux temperature in methylene chloride,1,3-bis[[p-(dimethylamino)benzylidene]amino]-2-[2-(1-pyrrolidinyl)vinyl]imidazoliumchloride of melting point 260° (decomposition);

(e) morpholine-4-carboxaldehyde diethyl acetal, there is obtained after4 days at reflux temperature in methylene chloride,1,3-bis[[p-(dimethylamino)benzylidene]amino]-2-(2-morpholinovinyl)imidazoliumchloride of melting point 259°-260° (decomposition);

(f) piperidine-1-carboxaldehyde diethyl acetal, there is obtained after4 days at reflux temperature in methylene chloride,1,3-bis[[p-(dimethylamino)benzylidene]amino]-2-(2-piperidinovinyl)imidazoliumchloride of melting point 240° (decomposition);

(g) 4-methylpiperazine-1-carboxaldehyde diethyl acetal, there isobtained after 6 days at 60° in dimethylformamide,1,3-bis[[p-(dimethylamino)benzylidene]-amino]2-[2-(4-methyl-1-piperazinyl)vinyl]imidazoliumchloride of melting point 256°-258° (decomposition).

EXAMPLE 16

(a) In analogy to Example 1c, from 1,3-diamino-2-methylimidazoliumchloride and 2,6-dimethyl-4-(dimethylamino)benzaldehyde, there isobtained1,3-bis[[4-(dimethylamino)2,6-dimethylbenzylidene]amino]-2-methylimidazoliumchloride of melting point 216°.

(b) In analogy to Example 15(a), from1,3-bis[[4-(dimethylamino)-2,6-dimethylbenzylidene]amino]-2-methylimidazoliumchloride and N,N-dimethylformamide diethyl acetal, there is obtainedafter 4 hours at room temperature in 1-propanol,1,3-bis[[4-(dimethylamino)-2,6-dimethylbenzylidene]-amino]-2-[2-dimethylamino)vinyl]imidazoliumchloride of melting point 230°-235° (decomposition):

EXAMPLE 17

73.5 g of N,N-dimethylformamide diethyl acetal are added to 20.5 g of1,3-bis[[p-(dimethylamino)benzylidene]amino]-2-methylimidazoliumchloride in 400 ml of dry dimethylformamide. After stirring at 50° for 4days, the mixture is left to cool. Then, 250 ml of ether are addedthereto and the product is removed by filtration and is recrystallizedfrom dry ethanol. There is obtained 1,3-bis[[p-(dimethylamino)benzylidene]amino]-2-[2-(dimethylamino)vinyl]imidazolium chloride ofmelting point 265° (decomposition).

EXAMPLE 18

(a) 32.8 g of sodium hydride (55 percent dispersion in oil) are washedwith absolute tetrahydrofuran. A solution of 53.1 g of 2-phenylimidazolein 1500 ml of N-methylpyrrolidone is then added dropwise thereto at 0°.The mixture is stirred at 0° for a half hour and at room temperature forabout 1.5 hours (until gas evolution is no longer to be observed). Then,85 g of O-diphenylphosphinylhydroxylamine are added thereto. The mixtureis stirred at room temperature for 20 hours and subsequently 910 ml ofwater are added thereto. The dark solution is stirred at roomtemperature for 1 hour and then extracted seven times with 300 ml ofdichloromethane each time. The extract is dried over sodium sulfate andevaporated. The residual oil is placed on a column loaded with 900 g ofsilica gel, whereupon the 1-amino-2-phenylimidazole is eluted withdichloromethane/ethanol (85:15).

In an analogous manner, from 2-(p-chlorophenyl)imidazole, there isobtained 1-amino-2-(p-chlorophenyl)imidazole of melting point 160°(ethanol/petroleum ether).

(b) 43.8 g of O-diphenylphosphinylhydroxylamine are added to 30.1 g of1-amino-2-phenylimidazole in 2000 ml of dichloromethane. After stirringat room temperature for 3 days an additional 21.9 g ofO-diphenylphosphinylhydroxylamine are added. After one day, the mixtureis filtered and the filter material is washed four times with 150 ml ofdichloromethane each time. The residue is placed on a column loaded with700 ml of ion-exchanger Amberlite IRA 400 (chloride), whereupon elutionis carried out with water. The eluate is evaporated and the residue istreated with ethanol and evaporated. After drying in a high vacuum overpotassium hydroxide, there is obtained 1,3-diamino-2-phenylimidazoliumchloride.

In an analogous manner, from 1-amino-2-(p-chlorophenyl)imidazole thereis obtained 1,3-diamino-2-(p-chlorophenyl)imidazolium chloride ofmelting point 210° (ethanol/ether; containing 7% ammonium chloride and1% water).

(c) 0.45 g of 1,3-diamino-2-phenylimidazolium chloride is dissolved in 6ml of glacial acetic acid. 0.64 g of 4-dimethylaminobenzaldehyde areadded thereto. After stirring for 24 hours, about 1 ml of absolute etheris added thereto. One day later the mixture is evaporated and theresidue is placed on a column loaded with 25 g of silica gel. Afterelution with dichloromethane/ethanol (98:2) and crystallization fromethanol/ether there is obtained1,3-bis[[p-(dimethylamino)benzylidene]amino]-2-phenylimidazoliumchloride of melting point 242°.

(d) In an analogous manner, from1,3-diamino-2-(p-chlorophenyl)imidazolium chloride there is obtained2-(p-chlorophenyl)-1,3-bis[[p-(dimethylamino)benzylidene]amino]imidazoliumchloride of melting point 242° (decomposition).

EXAMPLE 19

(a) 0.88 g of sodium hydride (55 percent dispersion in oil) is washedwith tetrahydrofuran. A solution of 1.72 g of 2-(2-phenylethyl)imidazolein 50 ml of N-methylpyrrolidone is then added dropwise thereto at 0°.The mixture is stirred at room temperature until gas evolution is nolonger to be observed. Then, 4.66 g of O-diphenylphosphinylhydroxylamineare added thereto. After stirring for 18 hours, 25 ml of water are addeddropwise thereto, whereupon the mixture is stirred at room temperaturefor an additional 1 hour. After the addition of 2 g of sodium chloride,the mixture is extracted with dichloromethane. The extract is dried oversodium sulfate and evaporated. The residue is taken up in methylenechloride/methanol/ether, whereupon the mixture is filtered andevaporated. There is obtained an oil which contains1-amino-2-(2-phenylethyl)imidazole.

(b) This oil (2.7 g) is treated with 50 ml of glacial acetic acid and2.98 g of p-dimethylaminobenzaldehyde. After standing at roomtemperature for 18 hours, the reaction solution is evaporated. Theresidue is placed on a column loaded with 200 g of silica gel. Theproduct is eluted with methyl acetate and crystallized fromdichloromethane/methanol/petroleum ether. There is obtained1-[[p-(dimethylamino)benzylidene]amino]-2-(phenylethyl)imidazole ofmelting point 153°-154°.

(c) 8.0 g of 1-bromo-3,3-dimethyl-butan-2-one are added to 0.64 g of1-[[p-(dimethylamino)-benzylidene]amino]-2-(phenylethyl)imidazole in 60ml of acetonitrile. After stirring for 24 hours, the product is removedby filtration. There is obtained3-[p-(dimethylamino)benzylidene]amino]-2-(phenylethyl)-1-(pivaloylmethyl)imidazoliumbromide of melting point 231°.

EXAMPLE A

1,3-Bis[[(p-dimethylamino)benzylidene]amino]-2-[2-(dimethylamino)vinyl]imidazoliumchloride is used in a known manner as the active substance for thepreparation of tablets of the following composition:

    ______________________________________                                                         mg/tablet                                                    ______________________________________                                        Active substance   100                                                        Lactose            192                                                        Maize starch       80                                                         Hydrolyzed maize starch                                                                          20                                                         Calcium stearate   8                                                          Tablet weight      400        mg                                              ______________________________________                                    

The compounds listed hereinafter can also be used as the activesubstance:

1,3-Bis[[(p-dimethylamino)benzylidene]amino]-2-(2-piperidinovinyl)imidazoliumchloride;

1,3-bis[[(p-dimethylamino)benzylidene]amino]-2-(2-morpholinovinyl)imidazoliumchloride;

1,3-bis[[(p-dimethylamino)benzylidene]amino-2-phenylimidazoliumchloride;

1,3-bis[[(p-dimethylamino)benzylidene]amino-2-(p-chlorophenyl)imidazoliumchloride;

3-[[p-(dimethylamino)benzylidene]amino]-1-(pivaloylmethyl)-2-(p-tolyl)imidazoliumbromide; and

3-[[p-(dimethylamino)benzylidene]amino]-1-(pivaloylmethyl)-2-(m-methoxyphenyl)imidazoliumbromide.

We claim:
 1. A compound of the formula ##STR16## wherein Q is a carbomono- or bicyclic aromatic group with two free valences which may beunsubstituted or substituted by one or two substituents selected fromthe group consisting of lower alkyl, lower alkoxy, lower alkylthio,lower alkanoyl, lower alkoxycarbonyl, phenyl, halogen, trifluoromethyl,hydroxy, nitro and cyano, the group --NR¹ R² is a basic amino grouprepresented by the formula --NRR' in which R is hydrogen or lower alkyland R' is a saturated lower hydrocarbon group which is unsubstituted orsubstituted by one or two lower alkoxy or hydroxy groups or by an amino,lower alkylamino, lower dialkyamino, oxo, lower alkoxycarbonyl or loweralkylenedioxy group, R³ is lower alkylthio, lower alkoxy or the group--(A)_(n) --Ra, n is the integer 0 or 1, A is vinylene or loweralkylene, Ra is a carbo mono- or bicyclic aromatic group which may beunsubstituted or substituted by one, two or three substituents selectedfrom the group consisting of di(lower alkyl)amino, lower alkyl, loweralkoxy, lower alkylthio, lower alkanoyl, lower alkoxycarbonyl, phenyl,halogen, hydroxy, trifluoromethyl, nitro and cyano, or a basic aminogroup represented by the formula --NRR' in which R is hydrogen or loweralkyl and R' is a saturated lower hydrocarbon group which isunsubstituted or substituted by one or two lower alkoxy or hydroxygroups or by an amino, lower alkylamino, lower dialkyamino, oxo, loweralkoxycarbonyl or lower alkylenedioxy group, R⁵ is hydrogen, loweralkyl, lower hydroxyalkyl, lower alkoxyalkyl, lower haloalkyl, a carbomono- or bicyclic aromatic group which may be unsubstituted orsubstituted by one, two or three substituents selected from the groupconsisting of di(lower alkyl)amino, lower alkyl, lower alkoxy, loweralkylthio, lower alkanoyl, lower alkoxycarbonyl, phenyl, halogen,hydroxy, trifluoromethyl, nitro and cyano or a fused benzene ring and R⁶is hydrogen or lower alkyl.
 2. A compound in accordance with claims 1,wherein R⁵ is hydrogen.
 3. A compound in accordance with claim 1,1-[[p-(dimethylamino)benzylidene]amino]-2-(p-tolyl)imidazole.